An object of this study is to understand those mechanisms which are responsible for the mediation of oxygen binding to the hemoproteins, hemoglobin, myoglobin and cytochrome P-450. Our approach involves the nuclear modulation effect in EPR as a means of discerning the interaction of unpaired spin of paramagnetic hemoproteins with remote nitrogen nuclei of imidazole ligands which are believed to electronically control electron density at the heme iron. This technique will be developed to study nuclear interactions that cannot be seen using conventional EPR techniques. For oxycytochrome P-450, the determination of the oxygen stretching frequency will define the oxidation state of the bound oxygen molecule. We should also like to devise a method based on EPR determination of zero field splitting of high spin ferric hemoproteins in order to ascribe structure of ligands on the basis of spin Hamiltonian parameters E and D. Studies of liver microsomal azoreductase will be used to elucidate electron transport mechanisms in microsomal systems. A major aspect of our study is to understand in depth both symmetry and bonding parameters for copper in model compounds and copper proteins. To this end, X-ray absorption spectroscopy will be used in concert with the linear electric field effect in EPR. Finally, studies on the toxicity of oxygen metabolites will be studied using two systems, red cell lysis and degradation of DNA.